Hypertriglyceridemia in equines treated with SGLT2 inhibitors

[EDITORS NOTE:
SGLT-2 inhibitors: sodium-glucose cotransporter-2 inhibitors

What are SGLT-2 inhibitors?
SGLT-2 inhibitor is an abbreviation for sodium-glucose cotransporter-2 inhibitors. SGLT-2 inhibitors are a class of medicine used to lower high blood glucose levels in people with type 2 diabetes. They may also be called gliflozins.

SGLT-2 inhibitors inhibit SGLT-2 proteins located in the renal tubules of the kidneys which are responsible for reabsorbing glucose back into the blood. As a result, more glucose is excreted in the urine. SGLT-2 inhibitors have been shown to be effective at lowering hemoglobin A1c levels, improving weight loss and lowering blood pressure. They carry a low risk of hypoglycemia (low blood sugar levels).

The use of SGLT-2 inhibitors in horses is experimental with no long term efficacy or safety studies. However, field studies have suggested a remarkable lowering of blood glucose and insulin levels in horses and other than the hypertriglyceridemia described here no adverse effects reported.

List of SGLT-2 inhibitors
Jardiance, Generic name: empagliflozin
Invokana Generic name: canagliflozin
Farxiga: dapagliflozin
Steglatro: ertugliflozin
Brenzavvy: bexagliflozin
]

Hypertriglyceridemia in equines with refractory hyperinsulinemia treated with SGLT2 inhibitors

Open Vet J. 2023 Mar;13(3):365-375. doi: 10.5455/OVJ.2023.v13.i3.14. Epub 2023 Mar 20.

Authors
Eleanor M Kellon 1 , Kathleen M Gustafson 1
Affiliation
1 Equine Cushing’s and Insulin Resistance Group, Inc, 2307 Rural Road, Tempe, AZ 85282, USA.
PMID: 37026076
PMCID: PMC10072834
DOI: 10.5455/OVJ.2023.v13.i3.14

Abstract
Background: Sodium-Glucose CoTransporter-2 (SGLT2) inhibitors, the -flozin group of drugs, which block glucose reuptake in the renal proximal tubule, are being increasingly used off-label to treat horses with refractory hyperinsulinemia. After 2 years of use by animals in our group, a horse on canagliflozin was incidentally noted to be hyperlipemic.

Case description: We have been following a cohort of equines (n = 20) treated with SGLT2 inhibitors due to refractory hyperinsulinemia. The animals are owned by members of the Equine Cushing’s and Insulin Resistance Group and treated by their attending veterinarians. The index case was a 23 years old gelding with a 2 years history of recurring laminitis that began canagliflozin therapy to control hyperinsulinemia which was no longer responsive to metformin. Between 6 and 10 weeks post start of therapy, significant weight loss was noticed. Two days later he was hospitalized with colic symptoms and hyperlipemia but was bright, alert, and eating well throughout. Canagliflozin was discontinued and triglycerides returned to normal reference values within 10 days. A subsequent study of 19 other horses on SGLT2 inhibitors revealed varying degrees of hypertriglyceridemia, all asymptomatic.

Conclusion: While this class of drugs holds great promise for cases of refractory hyperinsulinemia and laminitis that do not respond to diet or metformin therapy, hypertriglyceridemia is a potential side effect. In our experience, animals remained asymptomatic and eating well. Further study of hypertriglyceridemia in horses on SGLT2 inhibitors and the possible mitigating effect of diet is indicated. To our knowledge, this is the first report of hypertriglyceridemia with canagliflozin treatment in equines.

Keywords: Canagliflozin; Equine; Ertugliflozin; Hyperinsulinemia; Hypertriglyceridemia.